The inflammatory reaction to injury is complex, involving a massive response from the immune cells that guard and protect the body. These include fibroblasts in the local tissue, lymphocytes in lymph nodes and several other cells circulating in blood vessels. With injury to local tissue the smallest blood vessels in the area, capillaries, move cells into the tissue. These cells release inflammatory chemicals that attack damaged tissue and attract more cells from the capillaries. Fibroblasts are called into action and contribute to this inflammatory sequence that methodically destroys and devours damaged tissue. This battle that is mounted in our connective tissue system sends pain signals to the brain, where pain is perceived. That pain causes us to stop using that part of the body to allow it to finish the inflammatory activity.

Acute inflammation is the process that protects us every moment of our lives. Fibroblasts respond to injury or infection by stopping their usual function of tissue maintenance and repair. They transform in shape and produce inflammatory chemicals TNF-α, IL-1α, IL-1β, IL-6, IL-12. At the same time they release other chemicals that draw blood cells from local capillaries into the tissue. There they transform and produce more inflammatory chemicals. These combined inflammatory products destroy damaged tissue and invading microbes. They also devour the debris left behind, ultimately going back into the blood stream and carrying this debris away.Once the tissue is cleaned up, the anti-inflammatory response starts. It has its own sequence of events, starting with the release of chemicals that block current inflammatory chemicals and moving to a completely separate cascade that actively promotes anti-inflammation. This anti-inflammatory cascade leads to the return of normal maintenance and repair function of fibroblasts and guarding function of lymphocytes and other immune cells. Pain decreases and the brain sends instructions to restore normal use of this area.

The anti-inflammatory response follows the inflammatory response. Once blood cells carry off the debris of damaged tissue, anti-inflammatory chemicals, IL-10, IL-19, IL-22, IL-25, are released creating an active inflammatory cascade that reverses inflammation. Fibroblast Growth Factor is then released and Fibroblasts change shape and start making collagen again. This returns them to their main function of tissue maintenance and repair.In chronic inflammation several things happen to change all of this. Most importantly, the brain responds to pain signaling and ramps up pain from its normal state to excessive and persistent pain. Instead of using built in mechanisms to suppress pain, it uses neuroplastic processes to wind up and maintain it, even if local tissue damage in the body is repaired. These processes cause the brain’s own immune cells to release inflammatory chemicals, instructing wildly firing nerve cells in the pain pathway to release more of the main pain neurotransmitter, Substance-P. This expands the pain map and we perceive more pain. It also expands the loop between brain and body by sending much of that excess Substance-P down nerves into the peripheral body. Here, it is released into the already inflamed tissue, completely overwhelming the ability of the local tissue to block the inflammatory cascade and mount the anti-inflammatory process. Thus inflammation in local tissue goes on, regardless of whether or not the initial injury is resolved

Chronic inflammation begins the same way as acute inflammation. Fibroblasts respond to injury or infection by stopping their usual function of tissue maintenance and repair. They transform in shape and produce inflammatory chemicals TNF-α, IL-1α, IL-1β, IL-6, IL-12. For a number of reasons, including overwhelming infection, extensive tissue damage, inadequate immune response, this does not result in an anti-inflammatory response. Nerve cells in the pain circuit, start firing in a more intense and rapid manner. Long Tern Potentiation starts and local astrocytes and microglia produce their own inflammatory cascade. This keeps LTP going and the nerve cells produce more Substance-P. 20% is sent out of nerve endings and expands the pain circuit Map. More nerve cells are taken from other jobs to create more pain. 80% of the increased Substance-P is sent down nerve axons backwards through synapses and is released into already inflamed tissue. This dramatically increases local inflammatory responses and overwhelms any chance of establishing and anti-inflammatory response. This process sets up a vicious circle between brain and body.